Table 1.

Antibiotic agents to consider for treating diabetic foot osteomyelitis based on oral bioavailability and bone concentration (based on references [7,8,49,50]).

Infection Severity	Pathogens	Possible Antibiotics	Comments
Mild	Staphylococcus aureus (MSSA); Streptococcus spp. Methicillin-resistant S. aureus (MRSA)	Levofloxacin Amoxicillin-clavulanate Cephalexin Dicloxacillin Clindamycin Doxycycline Trimethoprim/ sulfamethoxazole	QD dosing; substandard for S. aureus Relatively broad spectrum & anti-anaerobic Requires QID dosing; inexpensive Narrow-spectrum; QID dosing; inexpensive Covers most (macrolide sensitive) MRSA & anaerobes MRSA, some gram-negatives; QD dosing MRSA, some gram-negatives; undefined against Streptococcus species
Moderate/Severe	MSSA; Streptococcus spp.; Enterobacteriaceae; obligate anaerobes MRSA Pseudomonas aeruginosa MRSA, Enterobacteriaceae, P. aeruginosa, anaerobes	Ertapenem * Ampicillin-sulbactam Imipenem-cilastatin (other carbapenems) Levofloxacin, or ciprofloxacin, with clindamycin Moxifloxacin Ceftriaxone Linezolid * Tigecycline Vancomycin Daptomycin Piperacillin-tazobactam * Vancomycin plus: - Piperacillin-tazobactam, or - Ceftazidime vs. cefepime, or - a carbapenem	QD dosing. Broad-spectrum anti-anaerobic; poor against Pseudomonas aeruginosa Relatively broad-spectrum but not for P. aeruginosa or other resistant gram-negatives Broad-spectrum; not active for MRSA; consider for proven/suspected ESBL producing pathogens Both oral and parenteral dosage forms suitable. Limited studies of clindamycin for severe S. aureus infections; possible anti-toxin effect QD doing. Broad-spectrum, including anaerobes QD dosing (IV or IM); 3rd gen. cephalosporin Oral and IV; adverse effects, drug interactions Broad-spectrum including MRSA; frequent gastrointestinal upset; less effective than others Narrow-spectrum; rising MICs in MRSA isolates QD-dosing; monitor CPK levels TID or QID dosing Very broad spectrum for empiric therapy in severe infections; narrow spectrum when culture & sensitivity results become available

MSSA: Methicillin-sensitive Staphylococcus aureus; MRSA: Methicillin-resistant Staphylococcus aureus; QD: Once daily; QID: Four times daily; IV: Intravenous; IM: Intramuscular; MICs: Mean inhibitory concentrations; CPK: Creatine phosphokinase; TID: Three times daily; * = Approved by the US Food & Drug Administration for treating diabetic foot infection.